Diabetes

Genetics
Copyright Genetics Society of America

Diabetes

Diabetes mellitus is a group of diseases characterized by elevated levels of glucose in the blood. Diabetes is caused by problems producing or responding to the hormone insulin. Insulin is produced in the pancreas by specialized cells called beta cells, in response to the presence of glucose absorbed through the gastrointestinal tract following a meal. Insulin promotes the uptake of glucose into muscle and fat cells, and it promotes the storage of excess glucose in the liver.

Excess blood glucose over time damages organs, particularly the eyes, kidneys, nerves, heart, and blood vessels. It is the leading cause of adult blindness, end-stage kidney disease, and lower limb amputations, and it is a major risk factor for heart attacks and strokes. Diabetes is classified into four major groups: type 1 diabetes (T1DM), type 2 diabetes (T2DM), other specific types, and gestational diabetes (GDM), occurring during pregnancy. Approximately 5 percent to 8 percent of the people of the industrialized world have diabetes, mostly (approximately 90 percent) type 2, which at least 16 million Americans have.

Type 1 Diabetes

Type 1 diabetes is caused by beta cell destruction, leading to insulin deficiency. T1DM was previously called insulin-dependent diabetes mellitus (IDDM), because patients who have it require insulin for survival. It was also called juvenile-onset diabetes mellitus, because most type 1 diabetics are children or young adults. At the time of diagnosis, about 85 percent to 90 percent of people with type 1 diabetes have antibodies directed against components of their beta cells, indicating that the immune system is responsible for the progressive and irreversible beta cell destruction.

Current evidence indicates a genetic component to T1DM. HLA (histocompatibility leukocyte antigen) genes are a group of genes on chromosome 6 that encode proteins that are part of the immune system. Normally the immune system defends the body against disease by destroying foreign
cells, but in the case of type 1 diabetes, the body's immune system destroys its own beta cells.

Certain types of HLA genes are strongly associated with type 1 diabetes, and other types protect against its development. However, these HLA genes are neither necessary nor sufficient to cause or protect from type 1 diabetes. T1DM is therefore a "complex" genetic disorder, in which several genes interact with the environment to result in the disease. Scientists are currently working to identify these other genes, as well as environmental factors (e.g., toxins and viruses) that provoke the development of T1DM.

Type 2 Diabetes

Type 2 diabetes is itself a group of disorders caused by some combination of insulin resistance—which occurs when cells' ability to respond to insulin is compromised—and insulin deficiency, which occurs when the beta cells' ability to make insulin is compromised. T2DM has, in the past, been called adult-onset diabetes, because most people with T2DM were adults. It was also called non-insulin-dependent diabetes mellitus (NIDDM), because people with type 2 diabetes usually do not require insulin injections. In the Unites States, T2DM is especially prevalent among certain ethnic minorities, including African Americans, Mexican Americans, Asian Americans, and Native Americans.

Obesity is a potent risk factor for T2DM. In the last thirty years, due to increased caloric intake and physical inactivity, both of which contribute to obesity, there was an explosion in the prevalence of T2DM, and it started occurring at younger ages—even in children. In addition to its association with an unhealthy lifestyle, T2DM is known to have a strong genetic component.

Scientists have been searching throughout the genome for T2DM-susceptibility genes. One such gene, calpain 10 protease, was identified on chromosome 2. A common variant of this gene may predispose certain individuals to T2DM; however, the true significance of this gene variant remains to be determined. In addition, several candidate genes have shown some evidence of being involved in T2DM. However, the effect of any single candidate gene variant on the risk of developing T2DM is modest. A candidate gene is a gene for which prior knowledge of its function leads researchers to assess whether chemical variation in it is associated with a disease.

As of 2002 there was no clinically available genetic test to predict the onset of type 2 diabetes, but it is anticipated that with a better understanding of the roles of various genes in T2DM, it will eventually be possible to use multiple genetic tests to identify individuals at risk for T2DM and to predict which treatments will be most helpful in specific patients. Although genetic susceptibility plays an important role in determining the risk of developing T2DM, studies have shown that the disease can often be prevented through diet, physical activity, and weight loss.

Other Specific Types of Diabetes

The third category of diabetes, containing other specific types, includes nongenetic forms as well as single-gene forms of diabetes. One group of single-gene diabetes disorders are genetic defects in beta cell function. The
most common of the genetic beta cell defects are the disorders known as MODY, or maturity onset diabetes of the young. MODY constitutes no more than 2 percent to 5 percent of all cases of diabetes. It often occurs in children and young adults and is characterized by decreased but not absent insulin production. It is inherited in an autosomal dominant manner, which means that an affected person has a 50 percent chance of passing on the disease-version of the gene with each pregnancy. Most, but not all, people receiving a MODY gene do develop diabetes.

There are at least six different genetic forms of MODY. MODY2 is caused by a mutation in a gene on chromosome 7 that makes a protein called glucokinase, which is an enzyme in beta cells that helps to provide a chemical signal needed for insulin release. The other MODYs involve mutations in genes that encode proteins called transcription factors, which allow beta cells to develop and function properly. These are hepatocyte nuclear factor 4-alpha (HNF4-alpha, causing MODY1, on chromosome 20), HNF1-alpha (causing MODY3, on chromosome 12), insulin promoter factor 1 (IPF1, causing MODY4, on chromosome 13), HNF1-beta (causing MODY5, on chromosome 17) and NeuroD1/beta2 (causing MODY6, on chromosome 2).

A very rare genetic insulin secretion disorder is maternally inherited diabetes and deafness (MIDD), caused by changes in the DNA of the mitochondria. The mitochondria are the energy powerhouses of the cell and the only part of the cell to contain DNA other than the nucleus, where most DNA is contained. MIDD and other mitochondrial disorders are maternally inherited because the fertilized egg has only mitochondria derived from the mother. The clinical features of MIDD can be similar to type 2 diabetes, and the hearing loss can be mild or even undetectable, except by special tests.

Another group of rare genetic diabetes types is characterized by extreme insulin resistance, which is defined as occurring when the ability of the body's cells to respond to insulin is severely compromised. Disorders of extreme insulin resistance include type A syndrome, leprechaunism, and Rabson-Mendenhall syndrome, and they are caused by inherited defects in the gene on chromosome 19 that makes the insulin receptor, a protein that allows cells to respond to insulin. Without properly functioning insulin receptors, insulin cannot work effectively. In addition to diabetes, individuals with insulin receptor defects may also have dental, genital, skin, and growth abnormalities. Most insulin receptor gene defects manifest in an autosomal recessive manner. That is, two defective copies of the gene are required for disease expression, and couples in which each partner has one defective copy (and in which neither is therefore affected) have a 25 percent chance of having an affected child, with each pregnancy.

Familial partial lipodystrophic diabetes (FPLD) is a rare condition in which children develop an unusual fat distribution at puberty, with little or no fat on their arms, legs, and trunk. They also develop insulin-resistant diabetes. FPLD is an autosomal dominant condition caused by mutations in the lamin A/C gene on chromosome 1. Another rare form of lipodystrophic diabetes is congenital (i.e., present at birth) generalized lipodystrophic (CGL) diabetes, which is autosomal recessive, and in about half of cases is due to mutations in the gamma-3-like gene (GNG3 ; also called the seipin gene), on chromosome 11.

Wolfram syndrome is a rare autosomal recessive condition presenting in childhood that includes diabetes mellitus as well as other problems, including deafness and deficiency of antidiuretic hormone. Mutations in the wolframin gene on chromosome 4 are responsible for some cases, but other cases appear to be caused by a gene in a different area of chromosome 4.

Another rare autosomal recessive childhood condition, thiamine-responsive megaloblastic anemia syndrome (TRMA), consists of several features, including blood abnormalities, deafness, and diabetes. TRMA, which responds to treatment with thiamine (a form of vitamin B), is a disorder caused by mutations in the thiamine transporter gene SLC19A2, on chromosome 1.

Transient neonatal diabetes (TNDM) is a condition in which infants are born requiring injected insulin but are able to make sufficient insulin later in infancy. Later in childhood or in adulthood, they may again develop diabetes, which may or may not require insulin treatment. Most cases of transient neonatal diabetes appear to be caused by the inheritance of an extra copy of a region of chromosome 6 from the father.

Many known genetic disorders other than those mentioned previously are associated with an increased risk of diabetes. Among those most strongly associated are Friedreich's ataxia, cystic fibrosis, and hemochromatosis.

Gestational Diabetes Mellitus

Hormones associated with pregnancy may cause diabetes in susceptible individuals. Although the diabetes goes away after the pregnancy, individuals who have had GDM are at increased risk of developing T2DM. Currently very little is known about the genetic basis of GDM. It is possible that some of the same genes responsible for T2DM are also involved in GDM.

Genetic Susceptibility to Complications

As mentioned above, diabetes is associated with complications involving the eyes, kidneys, blood vessels, and heart. However, not all individuals with diabetes develop these complications. There is increasing evidence that there are genes other than those that increase susceptibility to developing the disease that may influence susceptibility to developing its complications. These genes are not yet identified, but they are likely to interact with other known risk factors for complications, including poor blood-sugar control and increased blood-pressure and blood-cholesterol levels.

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diabetes

The Columbia Encyclopedia, 6th ed.

Copyright The Columbia University Press

diabetes or diabetes mellitus (məlī´təs), chronic disorder of glucose (sugar) metabolism caused by inadequate production or use of insulin, a hormone produced in specialized cells (beta cells in the islets of Langerhans) in the pancreas that allows the body to use and store glucose. It is a leading cause of death in the United States and is especially prevalent among African Americans. The treatment of diabetes was revolutionized when F. G. Banting and C. H. Best isolated insulin in 1921.

The Disorder

The lack of insulin results in an inability to metabolize glucose, and the capacity to store glycogen (a form of glucose) in the liver and the active transport of glucose across cell membranes are impaired. The symptoms are elevated sugar levels in the urine and blood, increased urination, thirst, hunger, weakness, weight loss, and itching. Prolonged hyperglycemia (excess blood glucose) leads to increased protein and fat catabolism, a condition that can cause premature vascular degeneration and atherosclerosis (see arteriosclerosis). Uncontrolled diabetes leads to diabetic acidosis, in which ketones build up in the blood. Patients have sweet-smelling breath, and may suffer confusion, unconsciousness, and death. There are two distinct types of diabetes mellitus: insulin-dependent and noninsulin-dependent.

Insulin-dependent Diabetes

Insulin-dependent diabetes (Type I), also called juvenile-onset diabetes, is the more serious form of the disease; about 10% of diabetics have this form. It is caused by destruction of pancreatic cells that make insulin and usually develops before age 30. Type I diabetics have a genetic predisposition to the disease. There is some evidence that it is triggered by a virus that changes the pancreatic cells in a way that prompts the immune system to attack them. The symptoms are the same as in the non-insulin-dependent variant, but they develop more rapidly and with more severity. Treatment includes a diet limited in carbohydrates and saturated fat, exercise to burn glucose, and regular insulin injections, sometimes administered via a portable insulin pump. Transplantation of islet cells has also proved somewhat successful since 1999, after new transplant procedures were developed, but the number of pancreases available for extraction of the islet cells is far smaller than the number of Type I diabetics. Patients receiving a transplant must take immunosuppressive drugs to prevent rejection of the cells, and many ultimately need to resume insulin injections, but despite that transplants provide real benefits for some whose diabetes has become difficult to control.

Noninsulin-dependent diabetes

Noninsulin-dependent diabetes (Type 2), also called adult-onset diabetes, results from the inability of the cells in the body to respond to insulin. About 90% of diabetics have this form, which is more prevalent in minorities and usually occurs after age 40. Although the cause is not completely understood, there is a genetic factor and 90% of those affected are obese. As in Type I diabetes, treatment includes exercise and weight loss and a diet low in total carbohydrates and saturated fat. Some individuals require insulin injections; many rely on oral drugs, such as sulphonylureas, metformin, acarbose or another alpha-glucosidase inhibitor, thiazolidinediones, or dipeptidyl peptidase–4 (DPP-4) inhibitors.

Complications

Diabetes affects the way the body handles fats, leading to fat accumulation in the arteries and potential damage to the kidneys, eyes, heart, and brain, and statins (cholesterol-lowering drugs) may be prescribed to prevent heart disease. It is the leading cause of kidney disease. Many patients require dialysis or kidney transplants (see transplantation, medical). Most cases of acquired blindness in the United States are caused by diabetes. Diabetes can also affect the nerves, causing numbness or pain in the face and extremities. A complication of insulin therapy is insulin shock, a hypoglycemic condition that results from an oversupply of insulin in relation to the glucose level in the blood (see hyperinsulinism).

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diabetes

diabetes There are two distinct conditions: diabetes insipidus and diabetes mellitus. The latter condition is more common, and is generally referred to simply as diabetes or sugar diabetes. Haemochromatosis is known as bronze diabetes.

Diabetes insipidus is a metabolic disorder characterized by extreme thirst, excessive consumption of liquids and excessive urination, due to failure of secretion of the antidiuretic hormone.

Diabetes mellitus is a metabolic disorder involving impaired metabolism of glucose due to either failure of secretion of the hormoneinsulin (insulin‐dependent diabetes) or impaired responses of tissues to insulin (non‐insulin‐dependent diabetes). If untreated, the blood concentration of glucose rises to abnormally high levels (hyperglycaemia) after a meal and glucose is excreted in the urine (glucosuria). Prolonged hyperglycaemia may damage nerves, blood vessels, and kidneys, and lead to development of cataracts, so effective control of blood glucose levels is important.

Type I diabetes mellitus develops in childhood (juvenile‐onset diabetes) and is due to failure to secrete insulin, and hence is called insulin‐dependent diabetes. Treatment is by injection of insulin (originally purified from beef or pig pancreas, now biosynthetic human insulin), together with restriction of the intake of sugars.

Type II diabetes mellitus generally arises in middle age (maturity‐onset diabetes) and is due to resistance of the tissues to insulin action; secretion of insulin by the pancreas may be normal or higher than normal. It is referred to as non‐insulin‐dependent diabetes and can sometimes be treated by restricting the consumption of sugars and reducing weight, or by the use of oral drugs which stimulate insulin secretion and/or enhance the insulin responsiveness of tissues (sulphonylureas and biguanides). It is also treated by injection of insulin to supplement secretion from the pancreas and overcome the resistance. Impairment of glucose tolerance similar to that seen in diabetes mellitus sometimes occurs in late pregnancy, when it is known as gestational diabetes. Sometimes pregnancy is the stress that precipitates diabetes, but more commonly the condition resolves when the child is born.

Renal diabetes is the excretion of glucose in the urine without undue elevation of the blood glucose concentration. It is due to a reduction of the renal threshold which allows the blood glucose to be excreted. See also glucose tolerance.

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diabetes

diabetes usually refers to the condition known in full as diabetes mellitus. ‘Diabetes’ can be translated, from its Greek derivation, as ‘going through’ — describing the characteristic copious production of urine. ‘Mellitus’ comes from the Latin for honey. There is an excess of sugar (glucose) in the blood and this ‘spills over’ into the urine, bringing an excess of water with it. The cause is either a deficiency of production of the hormone insulin by the pancreas, or defective response of body cells to the action of this hormone, which normally enables glucose and other nutrients to be taken up from the circulating blood. The derangement of metabolism leads to extensive complications. The type of diabetes due to lack of insulin production was fatal before the early 1920s, when treatment with an extract from animal pancreatic tissue was shown to be effective.

The illness with ‘the passing of too much urine’ was known in 1500 bc to the Egyptians; Aretaeus wrote of it in the second century ad as ‘diabetes … a melting down of the flesh and limbs into urine’; Paracelsus described it in the sixteenth century; but it was the English physician Thomas Willis who first reported in 1679 that the urine was ‘so wonderfully sweet’.

A much rarer condition, diabetes insipidus (with copious urine which is not ‘sweet’), is caused by deficiency of antidiuretic hormone (ADH) (also known as vasopressin) from the pituitary gland. ADH normally acts in the kidneys to prevent any greater escape of water in the urine than is necessary to maintain constancy of the salt concentration and volume of the body fluids. When ADH is lacking, due to disease or injury in or near the pituitary gland, the daily output of dilute urine can be 25–30 litres, with extreme thirst to match.

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diabetes

diabetes (dy-ă-bee-teez) n. any disorder of metabolism causing excessive thirst and the production of large volumes of urine. d. insipidus a rare form of diabetes that is due to deficiency of the pituitary hormone vasopressin (antidiuretic hormone). d. mellitus (DM) a disorder of carbohydrate metabolism in which sugars in the body are not oxidized to produce energy due to lack of the pancreatic hormone insulin. The accumulation of sugar leads to its appearance in the blood (hyperglycaemia), then in the urine; symptoms include thirst, loss of weight, and the excessive production of urine. The use of fats as an alternative source of energy leads to disturbances of the acid-base balance and ketosis (see (diabetic) ketoacidosis) and eventually to diabetic coma. The diet must be controlled, with adequate carbohydrate for the body's needs; lack of balance in the diet leads to hypoglycaemia. In type 1 (or insulin-dependent) d. mellitus, which usually starts in childhood or adolescence, patients are entirely dependent on injections of insulin for survival. In type 2 (noninsulin-dependent or maturity-onset) d. mellitus, either the pancreas retains some ability to produce insulin, but this is inadequate for the body's needs, or the body becomes resistant to the effects of insulin; oral hypoglycaemic drugs or insulin may be required. Type 2 diabetes usually occurs after the age of 40, but a rare form, maturity-onset d. of the young (MODY), develops in people under 25. gestational d. diabetes mellitus or impaired glucose tolerance that is diagnosed during pregnancy. —diabetic (dy-ă-bet-ik) adj., n.www.diabetes.org.uk Website of Diabetes UK

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diabetes

diabetes Disease characterized by lack of insulin needed for sugar metabolism. This leads to hyperglycaemia and an excess of sugar in the blood. Symptoms include abnormal thirst, over-production of urine and weight loss; degenerative changes occur in blood vessels. Untreated, the condition progresses to diabetic coma and death. There are two forms of the disease. Type 1 usually begins in childhood and is an autoimmune disease. Those affected owe their survival to insulin injections. Type 2 diabetes mostly begins in middle-age; there is some insulin output but not enough for the body's needs. The disease is managed with dietary restrictions, tablets to lower blood sugar levels and insulin injections. Susceptibility to diabetes mellitus is inherited and more common in males.

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Diabetes mellitus is a condition that results when the pancreas produces little or no insulin, or when the cells of the body cannot use the insulin produced effectively. When insulin is absent or ineffective, the cells of the body cannot absorb glucose (sugar) from blood to provide the body with energy.

Melinda had just turned twelve and felt hungry all the time. Her stomach growled in class and her after-school snack no longer held her until dinner. No matter how many trips she made to the school water fountain, she was always thirsty. Even worse, she could not believe how often she needed to go to the bathroom. One of her teachers, after signing Melinda’s seventh bathroom pass for the day, suggested that Melinda ask her parents to take her to the doctor. She thought that Melinda might have diabetes, and she was right.

Diabetes is a group of related diseases characterized by elevated levels of glucose (sugar) in the blood. It is caused by the failure of the pancreas to produce sufficient insulin, or any insulin at all. It can also be caused by the failure of the body’s cells to make proper use of the insulin that is produced.

The pancreas, the site of insulin production, is a large gland near the stomach. It contains groups of cells that function like tiny factories, producing different hormones* at exactly the right time and in the right amount. These groups (or “islands”) of cells are called islet (EYE-let) cells.

are chemicals that are produced by different glands in the body. Hormones are like the body’s ambassadors: they are created in one place but are sent through the body to have specific regulatory effects in different places.

One type of islet cell is called a beta (BAY-ta) cell. Beta cells are responsible for producing a hormone called insulin. The human body needs insulin to function, because insulin helps the body use food for energy.

When people eat, their bodies break food down and convert it into sugars and other fuels. The main fuel is a sugar called glucose (GLOO-kose). When it is in the blood, it is called “blood glucose” or sometimes “blood sugar.” Glucose provides the energy people need to carry out almost every task, from pumping blood to walking to reading a book. But glucose cannot get too far on its own—insulin must be there to allow it to pass into the body’s cells.

Insulin works like a key, “unlocking” the door to cells. When insulin production stops or slows down in the beta cell factory, the body’s cells cannot take in the glucose they need for energy. People with diabetes get glucose from their food, but no matter how much they eat, if the insulin “key” is absent or not working properly, their glucose fuel is “locked out” of the body’s cells.

More than fifteen million people in the United States have diabetes, but fewer than one million of those people (about 750,000) have the type that Melinda has. This type is known as Type 1 diabetes. It is also called immune-mediated diabetes or insulin-dependent diabetes mellitus (IDDM).

Type 1 diabetes is usually diagnosed before a person turns 19, and is therefore also referred to as “juvenile” diabetes. About 125,000 children and teenagers in the United States today have Type 1 diabetes. They make little or no insulin of their own, so they depend on injections of insulin to stay healthy. They also need to make lifestyle changes, such as when and what they eat.

The other fourteen-plus million Americans with diabetes have what is called Type 2 diabetes. Other names for this kind of diabetes include non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. Type 2 diabetes occurs when the cells of the body do not respond to insulin the way they should. This type of diabetes usually affects people who are over 40 years old. Extra body fat often contributes to this condition and, many times, weight loss can help remedy it. A person with Type 2 diabetes is not necessarily dependent on insulin injections the way a person with Type 1 diabetes is. Type 2 diabetes can also be treated with pills in addition to a change in diet.

Type 1 diabetes

Type 1 diabetes is not contagious like a cold or chickenpox: people cannot catch it from one another. Nor do people get Type 1 diabetes suddenly. It usually takes months or years to develop in a person’s body. Despite what many people think, Type 1 diabetes isn’t caused by eating too many sweets.

Although scientists do not know exactly what causes Type 1 diabetes, they have enough evidence to suggest that there are at least a couple of different reasons why one person might develop it while another would not: genes and environmental triggers.

Genes. People with Type 1 diabetes are born with certain genes for the illness, just as they are born with genes for blue eyes or brown eyes. Genes are something people inherit from their parents before they are born. In some families, the genes for Type 1 diabetes are passed from parents to more than one child; a sibling of someone with Type 1 diabetes has about a 5 percent chance of also developing it.

Environmental triggers. Some people have Type 1 diabetes set in motion by an environmental trigger, like a virus. The trigger will make the person’s immune system attack and destroy the beta cells, with the result that insulin can no longer be produced. However, for an environmental trigger to have this effect, people probably have to have a genetic predisposition to it. Most people do not just suddenly develop diabetes because they get the flu.

Type 2 diabetes

Just as with Type 1 diabetes, people with Type 2 diabetes are not contagious. Two major factors seem to play a role in why people develop Type 2 diabetes: genes and obesity (or being overweight).

Genes. Just as certain genes may mean that a person may be more likely to develop Type 1 diabetes, other genes play an important part in people who develop Type 2 diabetes.

Obesity. Many people who have Type 2 diabetes are obese. Scientists think that this extra weight may impair the body’s ability to use insulin effectively.

Symptoms

When the body does not have adequate amounts of insulin, symptoms like Melinda’s result. Frequent urination is very common in a person with Type 1 diabetes. This happens because glucose cannot get into the body’s cells and builds up in the blood instead. Normally, the kidneys do not allow glucose to get into the urine. But in the case of diabetes, the high level of blood glucose spills into the urine, pulling extra water out of the body along with it.

Feeling very thirsty is also common, because the body needs to make up for all the liquid lost through urination. Feeling hungry and eating a
lot are also common symptoms; the body is looking for a way to get the energy that it is missing. But even with all the extra eating, people with undiagnosed diabetes may lose weight, because their bodies start to use fat for energy instead of sugar. In the case of growing children and teenagers, the fact that they are not gaining weight at a time in their lives when they should be may be a sign that diabetes may be present.

These symptoms are common to both Type 1 and Type 2 diabetes, although usually less severe in the latter. Type 2 diabetes may sometimes present with other symptoms, such as repeated or hard-to-heal infections, blurred vision, and dry, itchy skin. But often these symptoms are quite mild, and due attention is not paid to them.

Diabetes at a Glance

Diabetes Type

Treatment

Age

Type 1

insulin

babies to adults

Type 2

diet, exercise, pills; in some cases insulin

most common in overweight adults over 40, but increasing among children and young adults

Diagnosis

If a doctor suspects that a patient has diabetes, usually he or she will first do a urine test. The test is simple: it involves a small sample of the patient s urine and special strips of paper that are treated with a chemical to detect glucose. If the immersed strip shows that glucose is present, the doctor will want to confirm the test by checking the patient’s blood sugar with a blood test. If the doctor feels sure that there is too much glucose in the patient’s blood, further evaluation and testing will be done, and treatment will be started if the diagnosis of diabetes is confirmed.

Because people with Type 2 diabetes continue to make insulin that is functioning to a certain extent, they may develop symptoms over a period of months or years without facing immediate danger. They may

Two Millennia of Medicine

The ancient Greek physician Aretaeus (ar-e-TE-us) of Cappadocia (c. 81-c. 138) described diabetes as a “melting down of the flesh and limbs into urine.” Throughout history, many people with the disease died at an early age by wasting away, although the disease was probably not as prevalent in ancient times as it is now.

Treatments frequently involved dietary changes. Aretaeus recommended milks, cereals, and starches. In 1797, John Rollo recommended a meat diet high in proteins. These diets were not cures for diabetes, but they did allow people with diabetes to live longer than if they had remained on standard diets.

The first truly successful treatment for diabetes was finally made available in the 1920s when Frederick Banting, Charles Best, and John James Macleod first isolated insulin for use through therapeutic injections.

feel tired, worn out, or thirsty much of the time, without thinking that it could be diabetes. In many cases, Type 2 diabetes is actually discovered by accident, during a routine physical exam or screening blood or urine test.

Sports Stars with Type 1 Diabetes

These outstanding athletes were all diagnosed with Type 1 diabetes at an early age:

Jackie Robinson Robinson was the baseball immortal who broke the color barrier in 1947. In his 10-year career with the Brooklyn Dodgers, Robinson was a batting champion, the League MVP, and a member of six championship teams. He was elected to the Hall of Fame in 1962, his first year of eligibility.

Bobby Clarke The tenacious leader of hockey’s Philadelphia Flyers for 15 seasons, Bobby Clarke was first diagnosed with diabetes at the age of 15. Undeterred, he went on to win three Hart Trophies as league MVP.

Wade Wilson An NFL quarterback for over 16 years, beginning in 1981, Wilson led the Minnesota Vikings to three playoffs and the 1987 NFC Championship game.

A person who has been diagnosed with Type 1 diabetes needs to do a number of things to function well. These include taking insulin, following a food plan, exercising, monitoring blood glucose levels, and taking urine tests. All of these things contribute toward achieving the major goal: keeping the amount of glucose in the blood as close to normal as possible, so the person with diabetes stays healthy and feels good, now and in the future.

Insulin

People with Type 1 diabetes must get the correct amount of insulin into their blood. Different sources of insulin have been used to treat diabetes. Pork insulin is extracted from the pancreas of a pig, but human insulin does not come from the pancreas of a human. Instead, human insulin is synthetic. It is made in a laboratory, and is the type most commonly used to treat diabetes today.

Insulin comes in liquid form (dissolved in water) in a bottle and must be injected into the body. Unlike a lot of medications, insulin cannot be swallowed in pill form because the hormone insulin is a protein. Like other proteins, it would be digested and broken apart in the stomach, just like the protein contained in food.

Most people take insulin by using a needle to inject it into the layer of fat beneath the skin. The most common places where people take insulin are in their arms, legs, stomach, and hips—all places where people have some fat. The injection does not hurt very much, since the needle is very thin. Usually, a person needs to inject insulin this way two or more times a day, on a set schedule, coordinated with meals.

Some people with Type 1 diabetes use an insulin pump. It is about the same size as a beeper, with a small container filled with insulin. The insulin gets automatically “pumped” into the person’s body through a small tube attached to a needle inserted into the skin. The insulin is pumped in at a slow rate all the time, with an extra “boost” pumped in before meals to prepare the body for the incoming sugar.

However people with Type 1 diabetes take insulin, one thing stays constant: they must take insulin every single day to allow the body’s cells to take in and use glucose properly. They cannot take a break or decide to stop taking it, or they will become ill.

Food

Proper nutrition is a very important part of staying healthy—for everyone—and especially for a person with Type 1 diabetes. Since food affects how much glucose is in the blood, people with Type 1 diabetes must pay careful attention to the food they eat, how much they eat, and when they eat it. In particular, since carbohydrates are the body’s main source of glucose, many people with diabetes estimate the amount of carbohydrates in each meal to determine if they are getting the right amount of sugar.

All that does not mean that the eating habits of someone with diabetes are so very different from other people. The food itself can be the same as that eaten by most people. But in most cases, their meal plans must be on some sort of schedule, include snacks, and limit sweets because of the large amount of sugar they contain.

Exercise

Just like healthy eating, exercise is something that is important for everyone and especially for people with Type 1 diabetes. It was not too long ago that some doctors thought people with Type 1 diabetes should not exercise, but that opinion has changed. Exercise helps insulin work better to control the level of glucose in the blood. Exercise also helps keep people with diabetes at the right weight, and it helps maintain a healthy heart and blood vessels. In addition, exercise helps people feel good about themselves.

When people with Type 1 diabetes exercise, they use glucose at a faster-than-normal rate, so they must pay special attention to ensure that their blood glucose level does not drop too low. This may mean taking less insulin, eating more before exercise, or having snacks during and after exercise.

Blood glucose and urine testing

People who have Type 1 diabetes usually test their blood glucose three or more times a day. This involves pricking the finger with a tiny, sharp device to get a drop of blood. The blood drop is put on a chemical strip and inserted into a testing meter that “reads” the amount of sugar in the blood. The person then records the blood glucose numbers in a diary. This monitoring helps to determine if the level of glucose in the blood is where it should be and guides adjustment in the treatment plan.

Urine testing is another helpful form of monitoring. It is especially important when a person with Type 1 diabetes is sick (with the flu, for example). Any kind of physical stress, such as an infection, tends to interfere with the body’s cells taking in and using glucose properly. When this happens, the cells begin to break down fat for energy. A potentially harmful byproduct of this process is the production of ketones*. Urine testing is an effective means of determining if ketones are building up in the blood.

Sometimes, even with insulin, proper nutrition, and exercise, it can be difficult to control diabetes completely. Blood glucose levels can become either too high or too low in some cases, and blood levels of ketones can rise to toxic levels.

Hypoglycemia

If the level of glucose in the blood is too low, this is called hypoglycemia (hy-po-gly-SEE-mee-a). This can result when someone takes too much insulin, misses a meal or snack, or exercises too hard without taking special precautions. In its beginning stages, hypoglycemia can make someone weak, shaky, dizzy, and sweaty. A person with diabetes learns to be very aware of these warning signs and almost always takes action

to treat them, by drinking some juice or taking glucose tablets, before they become severe. If left untreated, a person may become disoriented, sleepy, or have a hard time talking. Eventually, he may become very confused and uncoordinated and, in extreme cases, go into a coma*. The treatment for an extreme case of hypoglycemia is to give the person sugar as soon as possible, by intravenous* injection if necessary.

Clinical trials are research projects undertaken by scientists, pharmaceutical companies, and government researchers to investigate whether medications and treatment plans are safe and effective.

To evaluate the effectiveness of careful self-management in reducing the long-term complications of diabetes, in 1983 the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) undertook a large ten-year study, called the Diabetes Control and Complications Trial (DCCT for short).

People with diabetes took part in the DCCT and followed instructions for testing their blood glucose three or four times a day, taking more frequent insulin injections or using an insulin pump, and following a healthy meal plan. The test results showed that the people who maintained near-normal blood glucose levels had fewer long-term complications, such as problems with their hearts, eyes, or kidneys. It proved that for a person with diabetes, paying close attention to small things on a daily basis has a big payoff later on.

Hyperglycemia

Another problem that people with Type 1 diabetes can have is too much glucose in the blood, called hyperglycemia (hy-per-gly-SEE-mee-a). When there is too much sugar in the blood, it is often because the person has taken too little insulin, has eaten too much high-sugar food, or is ill with an infection or stressed for other reasons. Symptoms include very frequent urination, extreme thirst, weakness, and tiredness.

Ketoacidosis

In uncontrolled diabetes, when the blood becomes too acidic because of high levels of ketones in it, the condition that results is called ketoacidosis (ke-to-a-si-DO-sis). A person in ketoacidosis may be nauseated or vomiting and breathing very deeply. If he does not get treatment, he will become dehydrated and go into a coma. Emergency treatment involves insulin and lots of fluids, usually by intravenous injection. Fortunately, ketoacidosis is almost always preventable in people whose diabetes has been diagnosed, and who take care to manage their diabetes properly.

People who have Type 2 diabetes are often able to treat their diabetes with dietary changes and a weight-control program, if needed. This consists of balancing a healthy combination of foods and exercise.

In some cases, people with Type 2 diabetes are treated with pills. These pills do not contain insulin, but they help the body to make more insulin or respond to insulin more normally. Sometimes, a person with Type 2 diabetes will need to take insulin injections, like a person with Type 1 diabetes.

There are many similarities in the treatments for Type 1 and Type 2 diabetes, but the main difference is the role of insulin. If a person with
Type 2 diabetes forgets to take his insulin, he will not go into ketoacidosis. And while a doctor might say it is all right for a person with Type 2 diabetes to stop taking insulin completely and just take pills, this would not be possible for a person with Type 1 diabetes.

The U.S. and the World

Globally, there were approximately 135 million adults with diabetes in 1995. By the year 2025, that number is expected to rise to 300 million.

By the year 2025, it is estimated that the number of person’s with diabetes will be over 57 million in India, 37 million in China, and 22 million in the United States.

In 1997, there were more than 15 million people with diabetes in the U.S. Of those, more than 5 million had not been diagnosed.

Over 90 percent of diabetes cases are Type 2 diabetes. While Type 1 (the type that affects most children and teenagers with diabetes) is most common in Americans of European descent, the prevalence of Type 2 diabetes is 2 to 4 times higher in Americans of African, Hispanic, and Asian heritage. The highest incidence of all is among Native Americans.

In 1997, the average cost of health care for each American with diabetes was over $10,000 per year, compared to approximately $2,500 per year for Americans without diabetes.

Between taking insulin, following a meal plan, testing blood sugar levels, and the rest, living with Type 1 diabetes can sound like a big job—and it can be—especially in the beginning. Luckily, many people who have been diagnosed with Type 1 diabetes have an entire diabetes treatment team to help them along. This team usually includes a doctor, a diabetes nurse, a dietician, a psychologist, and a social worker. Ideally, the entire team works to become partners with the patient and the patient’s family, so that they can maintain as normal a life as possible.

People with diabetes can do almost everything that people without diabetes can. They can:

go to school

play sports

spend time with friends

eat food at parties

do almost every kind of job

go to college

get married

A person with diabetes may have to eat an extra snack before competing in a track meet, or duck out of a party for a minute to take insulin, or have only a small bit of ice cream when everyone else is going for the Super Sundae. But people who control their diabetes lead normal lives. And women with diabetes who want to have babies can usually do so, with the support of their diabetes treatment team.

Both Type 1 and Type 2 diabetes can have negative long-term effects on a person’s health. These effects tend to develop very slowly and gradually. Because a person with diabetes may not process fat properly, there tends to be damage to the blood vessels in the body, which increases the chances for high blood pressure, heart attacks, and strokes. Diabetes can also have long-term effects on the eyes, because tiny blood vessels in the retina* become weakened. If these blood vessels burst, they can cause bleeding and scarring in the eye, or even blindness. The chance of nerve damage, and of developing kidney disease, is also increased in a person with diabetes. Finally, foot health can become an issue for people with diabetes: because the condition can affect circulation to the feet, small cuts or wounds can turn into serious infections without proper care.

is the back inner surface of the eyeball that plays a key role in vision. This surface contains millions of light-sensitive cells that change light into nerve signals that the brain can interpret.

People with diabetes can take steps to help prevent or lessen the effects of these long-term problems. Recent research has shown that blood sugar control is a key factor. It is very important for people with diabetes to have regular physical checkups, when a doctor can monitor blood pressure and foot health, check fat levels in the blood, and look for problems with the kidneys. Annual trips to the eye doctor are crucial for people with diabetes. If the ophthalmologist* discovers problems with the blood vessels in the retina, vision problems often can be prevented or lessened with laser surgery.

People with diabetes often wear metal tags or bracelets imprinted or inscribed with important medical information. In the event of an accident or diabetic coma, the information on the tag can alert medical personnel about the patient’s condition.

Some companies offer medical alert tags that have an identification number that is unique to the individual so that a doctor who doesn’t know the person can retrieve the patient’s medical history in the event of emergency.

While people with diabetes must depend on doctors and other medical professionals to help them, they can also do quite a bit to help themselves. Continued education about proper diabetes management is a key part of helping people with diabetes stay healthy.

Diabetes research is an active field. Much of the scientific work is concerned with insulin: how to get it into the body, or how to get the body to produce it on its own. Since insulin cannot be swallowed, researchers

Banting, Best, and the Dog With Diabetes

Two scientists and a dog may sound like characters in a movie, but it was just such a threesome who were involved in discovering insulin. Shortly after World War I had ended, a Canadian surgeon named Frederick Banting (1891–1941) became very interested in diabetes and how the pancreas functions in a person with diabetes. A neighborhood child had died from diabetes, and this helped pique Banting’s interest in making discoveries about the condition.

In his University of Toronto laboratory, assisted by a graduate student named Charles Best, Banting took out the pancreas glands of several dogs (which caused the dogs to develop diabetes), extracted their insulin, and began investigating the properties of insulin. Banting and Best discovered that insulin brought down the level of blood glucose in the dogs’ blood; the dogs who had their pancreas glands removed could now survive, as long as they had insulin injections. A famous photo was taken of the two scientists in 1921, and between them stands the very first dog with diabetes that was kept alive with insulin.

In 1923, Sir Frederick Banting and the Scottish scientist John James Macleod (1876–1935) were awarded the Nobel Prize for medicine and physiology for their discovery of insulin.

have been investigating other ways to get it into the bloodstream without an injection, such as eye drops, nasal sprays, and inhalers. They have also experimented with pancreas transplantation, as well as transplantation of the islet cells that make insulin. Until there is a cure for diabetes, however, people must live with it and control it using the information and equipment available to them now.

Greek Speak: A Diabetes Dictionary

Many English words come from Greek. These include many of the words used to describe diabetes, as well as the word “diabetes” itself.

Diabetes Greek for “passing through,” because Greek doctors noticed how much liquid people with diabetes drank, and how often they needed to urinate.

Mellitus Greek for “honey-like” or “sweet,” because it was noticed that the urine of people with diabetes smelled sweet, due to its high sugar content.

Insulin Greek for “island.” The groups of islet cells in the pancreas that are responsible for making insulin and other hormones look like tiny islands under a microscope.

Books

Betschart, Jean, and Susan Thorn. In Control: A Guide for Teens with Diabetes.Minneapolis: Chronimed Publishing, 1995.

Chase, H. Peter. Understanding Insulin Dependent Diabetes.Denver: The Guild of the Children’s Diabetes Foundation, 1995. Also available online at the website for the Barbara Davis Center for Childhood Diabetes.

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